Isoflurane Preconditioning Induces Neuroprotection by Attenuating Ubiquitin-Conjugated Protein Aggregation in a Mouse Model of Transient Global Cerebral Ischemia
Isoflurane Preconditioning Induces Neuroprotection by Attenuating Ubiquitin-Conjugated Protein Aggregation in a Mouse Model of Transient Global Cerebral Ischemia
复制标题
异氟烷预处理通过减弱短暂性全脑缺血小鼠模型中泛素缀合蛋白的聚集来诱导神经保护
DOI：
10.1213/ane.0b013e3181e45519
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发表时间：
2010-08-01
影响因子：
5.7
通讯作者：
Xiong, Lize
中科院分区：
文献类型：
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作者：
Zhang, Hao-Peng;Yuan, Li-bang;Xiong, Lize
背景技术背景：在这项研究中，我们试图澄清的作用，抑制泛素结合的蛋白质聚集形成的神经保护作用后，异氟烷预处理使用短暂的全脑缺血再灌注损伤小鼠模型。方法：将C57 BL/6小鼠随机分为3组（异氟烷预处理[IsoPC]组、对照[Con]组和假手术组，每组n = 24）。将IsoPC组和假手术组的小鼠置于小室中，用异氟烷（1.2%异氟烷，98%O2，1小时/天）预处理5天。Con组小鼠置于同一室中，但仅用氧气（98%O2，2%N2，1小时/天）预处理5天。IsoPC组和Con组于最后一天预处理后24 h行双侧颈总动脉夹闭20 min的全脑缺血模型。分别在再灌注后24和72小时通过神经学评估、免疫组织化学和Western印迹法评估总运动评分、海马CA 1区存活神经元数量以及结合型泛素或游离型泛素的表达水平。结果：IsoPC组运动功能评分明显优于Con组（P < 0.05）。形态学观察显示IsoPC组神经元结构较Con组好。异氟醚预处理组海马CA 1区存活神经元数较Con组明显增加（P < 0.05）。异氟醚预处理后海马CA 1区TUNEL阳性神经元数量明显减少。IsoPC组CA 1区结合型泛素染色密度显著低于Con组（P < 0.05），IsoPC组CA 1区结合型泛素表达低于Con组（P < 0.05）。结论：在短暂性全脑缺血再灌注损伤小鼠模型中，抑制泛素结合蛋白聚集可能在异氟烷预处理诱导脑缺血耐受中起重要作用。
BACKGROUND: In this study, we sought to clarify the role of inhibiting ubiquitin-conjugated protein aggregation in the formation of a neuroprotective effect after isoflurane preconditioning using a transient global cerebral ischemia-reperfusion injury mouse model. METHODS: C57BL/6 mice were randomly assigned to 3 groups (isoflurane preconditioning [IsoPC] group, control [Con] group, and sham group, n = 24 in each group). Mice in the IsoPC group and sham group were placed in a chamber and pretreated with isoflurane (1.2% isoflurane, 98% O2, 1 hour/day) for 5 days. Mice in the Con group were placed in the same chamber but pretreated with oxygen only (98% O2, 2% N2, 1 hour/day) for 5 days. Twenty-four hours after the last preconditioning day, bilateral common carotid artery occlusion was performed as a model of global cerebral ischemia for 20 minutes in the IsoPC group and Con group. The total motor scores, number of viable neurons in the CA1 region of the hippocampus, and expression levels of conjugated ubiquitin or free ubiquitin were assessed by neurological assessment, immunohistochemistry, and Western blotting (at 24 and 72 hours) after reperfusion, respectively. RESULTS: The total motor scores in the IsoPC group were better than the Con group (P < 0.05). Morphological observations showed that the IsoPC group had better neuron structure than in the Con group. The numbers of viable neurons in the CA1 region were significantly increased by isoflurane preconditioning compared with those in the Con group (P < 0.05). The numbers of TUNEL-positive neurons in the CA1 region were significantly decreased after isoflurane preconditioning. The density of conjugated ubiquitin staining in the CA1 region of the IsoPC group was significantly lower than in the Con group (P < 0.05) and the expression of conjugated ubiquitin in the IsoPC group was lower than in the Con group (P < 0.05). CONCLUSION: Inhibition of ubiquitin-conjugated protein aggregation may have an essential role in inducing cerebral ischemic tolerance by isoflurane preconditioning in a transient global cerebral ischemia-reperfusion injury mouse model.